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Biomedical subjects

C Dougherty

Publications and source records attributed to C Dougherty.

At least 19 recordsLinked to original sources
PubMed2001

Cytoprotection by Jun kinase during nitric oxide-induced cardiac myocyte apoptosis.

Nitric oxide (NO) induces apoptosis in cardiac myocytes through an oxidant-sensitive mechanism. However, additional factors appear to modulate the exact timing and rate of NO-dependent apoptosis. In this study, we investigated the role of mitogen-activated protein kinases (MAPKs) (extracellular signal-regulated kinase [ERK] 1/2, c-Jun N-terminal kinase [JNK] 1/2, and p38MAPK) in NO-mediated apoptotic signaling. The NO donor S:-nitrosoglutathione (GSNO) induced caspase-dependent apoptosis in neonatal rat cardiac myocytes, preceded by a rapid (<10-minute) and significant (approximately 50-fold) activation of JNK1/2. Activation of JNK was cGMP dependent and was inversely related to NO concentration; it was maximal at the lowest dose of GSNO (10 micromol/L) and negligible at 1 mmol/L. NO slightly increased ERK1/2 beginning at 2 hours but did not affect p38MAPK activity. Inhibitors of ERK and p38MAPK activation did not affect cell death rates. In contrast, expression of dominant-negative JNK1 or MKK4 mutants significantly increased NO-induced apoptosis at 5 hours (56.77% and 57.37%, respectively, versus control, 40.5%), whereas MEKK1, an upstream activator of JNK, sharply reduced apoptosis in a JNK-dependent manner. Adenovirus-mediated expression of dominant-negative JNK1 both eliminated the rapid activation of JNK by NO and accelerated NO-mediated apoptosis by approximately 2 hours. These data indicate that NO activates JNK as part of a cytoprotective response, concurrent with initiation of apoptotic signaling. Early, transient activation of JNK serves both to delay and to reduce the total extent of apoptosis in cardiac myocytes.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor.

Adenosine is an important mediator of the endogenous defense against ischemia-induced injury in the heart. Adenosine can achieve cardioprotection by mediating the effect of ischemic preconditioning and by protecting against myocyte injury when it is present during the infarct-producing ischemia. A novel adenosine A3 receptor can mediate this protective function. One approach to achieve cardioprotection is to enhance myocardial sensitivity to the endogenous adenosine by increasing the number of adenosine receptors instead of administering an adenosine receptor agonist. The objective of the present study was to investigate whether genetic manipulation of the cardiac myocyte, achieved by gene transfer and overexpression of the human A3 receptor cDNA, renders the myocytes resistant to the deleterious effect of ischemia. Prolonged hypoxia with glucose deprivation, causing myocyte injury and adenosine release, was used to simulate ischemia in cultured chick embryo ventricular myocytes. During simulated ischemia, cultured myocytes with enhanced expression of the human A3 receptor and showed significantly higher ATP content, fewer cells killed, and less creatine kinase released into the medium than either control or mock-transfected myocytes. Also, increased expression of the A3 receptor caused an enhanced cardioprotective effect by the preconditioning ischemia. Overexpressing the adenosine A1 receptor also led to increased protection against ischemia-induced myocyte injury as well as an enhanced preconditioning effect. Thus, increasing the receptor level improves the myocyte sensitivity to the endogenous adenosine, which in turn causes all of the cardioprotective effects found for exogenously administered adenosine agonists. The study provides the first proof for the new concept that an increased expression of the human A3 receptor in the cardiac myocyte can be an important cardioprotective therapeutic approach.

Adenosine↗
PubMed1998

Musculoskeletal transplant.

Allograft tissue has been used for more than two centuries in the repair of musculoskeletal injuries and defects. More than 150,000 procedures are performed each year in the United States alone, 10 times the number of organ transplants. Nurses caring for allograft recipients may be unfamiliar with where tissue comes from, how it is recovered, and the variety of its practical applications. Similar to the process of organ donation, with which many nurses have had experience, it all begins with the gift.

Bone Transplantation↗
PubMed1994

Core values in health care reform: a communitarian approach.

Controlling health care costs should allow the nation to provide more health services and higher quality care to more people. The authors are concerned, however, that many of the reform efforts will unwittingly undermine the culture of care in their pursuit of savings and access. This article is a plea to maintain the core moral values and the social and institutional commitments that are essential in the delivery of care, so that the health care community is not turned into a health industry. The authors' communitarian approach aims to preserve the balance between individual rights and social responsibilities, the moral integrity of a caring society, and the unique character of mutual trust between patients and health care personnel. They advocate an orientation toward preventing disease and promoting health, an imperative of reforming the violent, reckless, and costly aspects of American society, and a moral justification for cutting administrative waste, defensive medicine, and excessive profits rather than rationing beneficial and humane health services.

Child↗
PubMed1992

Predicting success on conditional release for insanity acquittees: regionalized versus nonregionalized hospital patients.

This research compared the outcomes of two cohorts of insanity acquittees: one group was treated solely in the maximum security state forensic hospital before their release to the community (nonregionalized) and the other group was treated at the state forensic hospital and transferred for further treatment at less secure state regional hospitals (regionalized). This research describes the outcome of a group of insanity acquittees (regionalized patients) never previously studied. The applicability of a prediction model based on earlier research of insanity acquittees was tested on the patients. Findings on four outcome indicators are reported: rearrests within five years after release, overall functioning in the community five years after release, rehospitalizations for mental illness, and successful completion of the terms of the five-year conditional release (nonrevocation). Discriminant analysis was performed on the four outcome variables. The model was found to accurately predict the four types of outcome from 69 percent to 94 percent accurately for the nonregionalized insanity acquittees and from 87.5 percent to 95.8 percent for the regionalized patients. This model is currently being adapted to classify patients into potential high- and low-risk groups at the time of conditional release for the purpose of determining the intensity of outpatient supervision.

Cohort Studies↗
PubMed1991

Twin pregnancy: the impact of the Higgins Nutrition Intervention Program on maternal and neonatal outcomes.

Perinatal outcomes were compared between 354 twins treated with the Higgins Nutrition Intervention Program and 686 untreated twins. After differing distributions of key confounding variables were adjusted for, the twins in the intervention group weighed an average of 80 g more (P less than 0.06) than the nonintervention twins; their low-birth-weight rate was 25% lower (P less than 0.05) and their very-low-birth-weight rate was almost 50% lower (P less than 0.05). Although the rate of preterm delivery was 30% lower in the intervention group (P less than 0.05), the rates of intrauterine growth retardation were similar in the two groups. Fetal mortality was slightly higher (14 vs 12 per 1000, NS), but early neonatal mortality was fivefold lower (3 vs 19 per 1000, P less than 0.06) in the intervention group. Maternal morbidity was significantly lower (P less than 0.05) in the intervention group. There was a trend towards lower infant morbidity in the intervention group. These results suggest that nutritional intervention can significantly improve twin-pregnancy outcome.

Birth Weight↗
PubMed1990

DRGs and the "negative" trauma workup.

We conducted a study to assess the financial impact of the diagnostic workup and care of 136 trauma patients admitted to our institution during a six-month period who were subsequently found to have only minor injuries (Injury Severity Score less than or equal to 9, Abbreviated Injury Score less than 3). The New Jersey DRG reimbursement system, an all-payer system, failed to provide adequate financial compensation overall, as the average loss per patient (operating cost minus reimbursement) was $508. Lost potential revenue (hospital charges minus reimbursement) was even greater, averaging $1,834 per patient. We conclude that the New Jersey DRG reimbursement system, in its current form, provides inadequate reimbursement for the system, in its current form, provides inadequate reimbursement for the proper workup and treatment of trauma patients with minor injuries. Because these patients are those most likely to help "subsidize" the care of sicker patients, changes in the system are necessary to allow hospitals to continue to provide state-of-the-art trauma care and to continue to minimize the number of preventable deaths due to trauma.

Adolescent↗
PubMed1989

Dose-related effects of intracoronary application of nisoldipine on central and peripheral circulatory parameters.

In a randomized study central and peripheral circulatory parameters were determined in 12 anaesthetized mongrel dogs before and after intracoronary injection of nisoldipine and placebo. Administration of 0.2 to 0.8 micrograms/kg nisolpine was followed by a 46% to 62% decrease in coronary vascular resistance and a 109% to 141% increase in myocardial blood flow lasting 10 min. There was no significant change in myocardial contractility or peripheral circulatory parameters. An increase in dosage to 1.6 micrograms/kg did not cause a further increase in myocardial blood flow or decrease in coronary vascular resistance. However, there was a significant decrease in total peripheral resistance of up to 32% and a 36% increase in heart rate attributable to counter-regulation lasting 3 to 5 min. At this dosage level a significant decrease in myocardial contractility and an increase in left ventricular end-diastolic pressure are to be expected. This implies a major dissociation between coronary vascular effects and changes in parameters of myocardial performance and peripheral resistance after intracoronary administration of nisoldipine, an effect which is dose-related. Injection of 0.4 to 0.8 micrograms/kg would seem to be the optimal dosage range for intracoronary administration of nisoldipine producing maximum coronary dilatation without myocardial depression.

Animals↗
PubMed1988

[Results and limits of fibrin-unspecific thrombolysis in acute myocardial infarct].

Acute myocardial infarction is caused by thrombotic occlusion of a coronary vessel. Mortality and quality of life are both determined by the extent of infarction. It is possible to interrupt the development of necrosis by early fibrinolytic therapy. If reperfusion is initiated within three to six hours, a significant reduction in mortality is likely. Currently available fibrin-unspecific plasminogen activators such as streptokinase and urokinase are effective thrombolytic agents but do not fulfill all the criteria of an ideal plasminogen activator. Recanalisation rates are relatively low after intravenous administration, since the agents are not fibrin-specific and because the effect is delayed. Serious hemorrhagic complications may occur, since therapeutically effective dosage results in a hemostatic defect. The possible advantages of reduction in blood viscosity for collateral circulation in the ischemic region and a possible antithrombotic effect have not been defined. A complex strategy is necessary for optimal treatment of acute myocardial infarction. Early intervention is decisive in regard to recanalisation rate, infarct size, left ventricular function and mortality, while delayed interventions serve to maintain the advantages of early recanalisation by limiting angina pectoris and preventing reinfarction. Therefore, a combination of early intravenous administration of a fibrinolytic agent with subsequent invasive intervention appears reasonable and advantageous. Progress in the treatment of acute myocardial infarction will depend on development of effective plasminogen activators capable of achieving rapid and complete recanalisation without major side effects after intravenous administration.

Coronary Circulation↗
PubMed1986

Effect of a methylxanthine preparation in the form of a retention enema on pulmonary function and theophylline levels in patients with acute bronchospasm.

The goal of the current study was to determine whether administration of a methylxanthine preparation in the form of a retention enema (theophylline-diprophylline-proxyphylline combination, Neobiphyllin-Clys) has an effect similar to that of intravenous theophylline in the treatment of acute bronchospasm. In a randomized cross-over study 16 patients with a history of asthma were given 0.48 g of theophylline-ethylenediamine (TE) in the form of rapid intravenous infusion or a retention enema containing 400 mg theophylline, 600 mg diprophylline and 600 mg proxyphylline (TDP). Forced expiratory volume in the first second (FEV1) airways resistance (Rt) and serum theophylline levels were determined before administration of the drug and at 15 min, 30 min and hourly for a period of 6 h after administration of the medication. The results were significant at the 5% level. There were significant increases in serum theophylline levels with both TE and TDP. After administration of TE there were significant changes in FEV1 at 15 min and Rt at 30 min which persisted for 5 h after administration of the drug. Statistically significant differences in FEV1 were observed 60 min and in Rt 30 min after administration of TDP. These effects persisted for 6 h. The data document that a retention enema offers the advantage of prolonged action in comparison to intravenous infusion of theophylline in the treatment of acute bronchospasm.

Airway Resistance↗
PubMed1985

Rapid accurate absolute granulocyte count determination during severe leukopenia using the flow cytometer.

The absolute granulocyte count (AGC) in 125 blood samples from patients with total white blood cell counts of less than 1,000/microliter was estimated using three different methods, which were then compared for efficiency and accuracy. The three methods were 25 cell differential counts using Wright's-stained blood smears, granulocyte percentage estimates from WBC counting chambers, and combined narrow- and wide-angle light-scatter characteristics determined on a flow cytometer. A survey of clinical laboratories at University Hospital Cancer Centers revealed that the smear differential was the most-often-used method in those laboratories even when less than 25 cells could be counted. Consequently the data obtained from the counting chamber and flow cytometer methods were compared to the smear differential "standard" using linear regression, and outliers were identified. There was good correlation between AGC determined by smear differential and WBC counting chamber (correlation coefficient .911) and excellent correlation between the AGC determined by smear differential and the flow cytometer method (correlation coefficient .970). The flow cytometer method used in this investigation required minimal specimen preparation, and test results were available at a rate of 60 seconds/sample. The ease of sample preparation, speed, and statistical reliability of test results makes the flow cytometer an attractive alternate method of determining granulocyte counts on leukopenic patients as compared to the stained blood smear differential.

Flow Cytometry↗
PubMed1985

Simultaneous reticulocyte and platelet counting on a clinical flow cytometer.

Laser flow cytometric analysis is well suited to many clinical immunofluorescent and hematologic applications. One of these is automated reticulocyte and platelet enumerations. We have performed a clinical evaluation of a fluorescence laser flow cytometer reticulocyte and platelet enumeration method using the fluorochrome acridine orange. One hundred and thirty-two clinical specimens from inpatients in our comprehensive cancer center were analyzed for platelet counts and 101 samples from the same population were analyzed for reticulocyte counts by the flow cytometer and simultaneously by conventional techniques. Both the reticulocyte and platelet enumerations achieved a high degree of correlation with standard methods for the nonbone marrow-transplant patients studied (R = .989 for reticulocytes and R = .995 for platelets). Marrow transplant patients had a slightly poorer correlation coefficient for the reticulocyte enumeration (R = .923), but analysis of serial determinations of these patients' samples for reticulocyte counts revealed that results were more consistent over time with the automated method than with the traditional manual method. The laser flow cytometer fluorescence reticulocyte and platelet enumeration methods described are efficient, rapid, and reliable for platelet and reticulocyte counting.

Acridine Orange↗
PubMed1985

Hemodynamic effects of molsidomine, isosorbide dinitrate, and nifedipine at rest and during exercise.

In the first study the hemodynamic effects of standard doses of molsidomine (2 mg intravenously), isosorbide dinitrate (ISDN) (5 mg sublingually), and nifedipine (20 mg sublingually) were assessed at rest and under exercise conditions in a group of 30 patients with coronary heart disease. With the patients at rest both molsidomine and ISDN were associated with prompt reductions in left ventricular end-diastolic pressure and mean pulmonary artery pressure, whereas nifedipine was associated with slight reductions in left ventricular end-diastolic pressure and mean pulmonary artery pressure that did not attain statistical significance. Nifedipine and ISDN caused a decrease in mean aortic blood pressure, which resulted in a reactive increase in heart rate that was only significant with nifedipine. After administration of molsidomine, there was no significant change in mean aortic pressure at rest. There were reductions in stroke volume index and cardiac index after administration of molsidomine and ISDN. Nifedipine, however, was associated with significant increases in stroke volume index and cardiac index. None of the three test substances caused changes of contractility parameters. Under exercise conditions reductions in left ventricular end-diastolic pressure, mean pulmonary pressure, and mean aortic pressure were documented following administration of molsidomine, ISDN, and nifedipine. There were no major changes in maximum heart rate or stroke volume index during exercise with any of the three drugs. However, nifedipine was associated with a significant increase in cardiac index, whereas molsidomine and ISDN produced no major changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Estimates of lifetime lung cancer risks resulting from Rn progeny exposure.

Data on five mining populations exposed to Rn progeny have been used to estimate the lifetime risk of lung cancer resulting from occupational and environmental exposure under current standards. Slopes of dose-response relations for lung cancer show a tendency to decrease with increasing dose. Our best estimate of curvilinearity is given by raising dose to the power 0.92 +/- 0.07, but the improvement in fit beyond simple linearity is not significant. On the other hand, the addition of a cell-killing term significantly improves the fit of the linear model. In any event, linear extrapolation is unlikely to underestimate the excess risk at low doses by more than a factor of 1.5. However, these inferences about curvilinearity are highly subject to error from the choice of reference populations, dosimetry, and latency. Under the linear-cell-killing model, our best estimate of excess relative risk is 2.28 +/- 0.35 per 100 working level month (WLM) (a doubling dose of 44 WLM). Attributable risks in these five studies range from 3.4-17.8 per 10(6) person-yr WLM-1. Risks from Rn progeny appear to interact with age and smoking in a form intermediate between additive and multiplicative. The "relative risk" model is therefore preferable for projecting lifetime risks, but life-table projections are described for a wide variety of assumptions. Our best estimate of the effect of a 50-yr occupational exposure to 4 WLM yr-1 is 130 excess lung cancer deaths per 1000 persons (0.65 per 1000 person-WLM), with a range from 60-250 per 1000. Similar calculations for lifetime exposure to an additional 0.02 working level (WL) beyond normal background produces an estimate of 20 excess lung cancers per 1000 persons.

Adolescent↗
PubMed1983

Do infant formula samples shorten the duration of breast-feeding?

To determine whether advertising by infant formula companies shortens the duration of breast-feeding, we randomly assigned 448 breast-feeding new mothers to either receive or not receive a formula sample packet upon discharge from a maternity ward. These mother, unaware of the study, were then telephoned 3 months post partum by a research assistant blind to the randomisation status. "Sample" mothers were less likely to still be breast-feeding at 1 month (78% vs 84%, p = 0.07) and more likely to have introduced solid foods by 2 months (18% vs 10%, p = 0.01). These trends became more significant in three vulnerable subgroups: less educated mothers, primiparas, and mothers who had been ill post partum. Our results suggest that infant formula samples may shorten the duration of breast-feeding and hasten the age at which solids are introduced.

Breast Feeding↗
PubMed1982

Flow cytometric characterization of the response of Fanconi's anemia cells to mitomycin C treatment.

DNA flow histogram analysis, using 33342 Hoechst as a stain, has been used to detect the effect of the potentially bifunctional alkylating agent, mitomycin C (MMC) on dermal fibroblasts from patients with Fanconi's anemia (FA), a hereditary human disease characterized by pancytopenia, hypersensitivity to DNA-crosslinking agents, congenital abnormalities and a predisposition for neoplasia. At 24 or 48 hr after a 2-hr exposure to 0.05 or 0.10 micrograms/ml MMC, (3)HdT incorporation was reduced to a greater extent in FA cells than in normal cells. Cells sorted from the last half of S phase showed a slightly greater inhibition of (3)HdT incorporation than did those sorted from the first half of S. Fanconi's anemia cells exhibited a marked accumulation in the G(2) + M peak of flow histograms following exposure to MMC. Twenty-four hr after treatment with .0.5 micrograms/ml MMC, the G(2) + M fraction of FA cells (eight lines) increased to more than 0.5 from a control value of approximately 0.02. Both normals (six lines) and heterozygotes (eight lines) showed, on the average, much less of a G(2) + M increment than did FA cells, even after exposure to 0.1 micrograms/ml MMC. Examination of cells sorted from the G(2) + M peak revealed that MMC-treated FA cells were blocked prior to mitosis. To determine whether the response of FA cells was specific for bifunctional alkylating agent, cells were also treated with ethylmethanesulfonate, a monofunctional agent. Twenty-four hours after exposure to 0.25 or 0.5 mg/ml ethylmethanesulfonate, FA and normal cells showed similar, small increases in the G(2) + M peak. The results suggest the utility of flow cytometry in the diagnostic evaluation of fibroblasts from patients suspected of having Fanconi's anemia.

Alkylating Agents↗
PubMed1982

Cytogenetic and flow cytometric studies of cells from patients with Fanconi's anemia.

Cells from patients wtih Fanconi's anemia are unusually sensitive to agents which are capable of crosslinking DNA. This increased sensitivity can be detected both by cytogenetic and flow cytometric methods. An elevated frequency of chromosome aberrations, which is further exaggerated by exposure of cells to DNA crosslinking agents, is a general feature of Fanconi's anemia. Information about the formation of sister chromatid exchanges in this disease is less consistent. Cytogenetic analysis of cells from patients with Fanconi's anemia can be compromised by a low mitotic index. This is reflected in an accumulation of cells In the G2 phase of the cycle, after exposure to the bifunctional alkylating agent, mitomycin C. New methods for differentiating individuals with Fanconi's anemia from unaffected individuals should be of empirical use and might also facilitate mechanistic studies of this disease.

Anemia, Aplastic↗